Design and Construction of Protein Molecules with Novel Properties

Abstract :

One of the most important challenges in chemical biology is to understand the molecular basis of protein function. Developing new methodologies using chemistry and the ability to apply those methodologies to proteins plays a crucial role in addressing this challenge. I propose to direct my future research program towards applying chemistry to design and engineer novel protein molecules, and to systematically develop a new class of therapeutics with controlled biochemical properties. Part of my research will be focused on the design and total chemical synthesis of medicinally relevant protein molecules with complex polypeptide backbone topologies that are rare or do not occur in natural proteins. I will develop a novel technology, using virtual structure-based screening of peptide fragment libraries from protein data bank, to identify small protein molecules of opposite handedness that will be used as candidate therapeutics. A significant portion of my research will be dedicated to develop and apply chemistry tools to enhance the conformational rigidity, introduced by the incorporation of fixed elements of secondary structures that will improve the stability and receptorbinding affinity of the small protein drug candidates. I will also explore and extend racemic and quasi-racemic crystallography to unravel complex biological questions. All these research projects will be pursued with the goal of addressing a wide range of questions having implications in fundamental as well as inapplied research.